Perfluorooctane sulfonate mediates secretion of IL-1β through PI3K/AKT NF-кB pathway in astrocytes
| Autor: | Kaizhi Yin, Jiashan Luo, Pingping Sun, Shengyang Jiang, Jiamin Mao, Yiming Liu, Xiaoke Nie, Yan Zhang, Lingli Sun, Xiaoxu Chen |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Morpholines Interleukin-1beta Cell Count Toxicology Phosphatidylinositol 3-Kinases 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine NF-KappaB Inhibitor alpha Developmental Neuroscience Glial Fibrillary Acidic Protein medicine Animals Protein kinase B Cells Cultured PI3K/AKT/mTOR pathway Fluorocarbons Dose-Response Relationship Drug Microglia Glial fibrillary acidic protein biology Chemistry NF-kappa B Transcription Factor RelA Rats Cell biology IκBα 030104 developmental biology medicine.anatomical_structure Alkanesulfonic Acids Chromones Astrocytes biology.protein Astrocytosis Signal transduction Proto-Oncogene Proteins c-akt 030217 neurology & neurosurgery Signal Transduction Astrocyte |
| Zdroj: | Neurotoxicology and Teratology. 67:65-75 |
| ISSN: | 0892-0362 |
| DOI: | 10.1016/j.ntt.2018.03.004 |
| Popis: | Perfluorooctane sulfonate (PFOS) is a persistent and bioaccumulative compound that has been widely used in various fields of life and industrial productions, because of its special chemical and physical properties. Numerous studies have indicated significant neurotoxic effect of PFOS, especially on neurons and microglia. However, the influence of PFOS on astrocyte physiology remains unclear. In this study, we showed that PFOS triggered reactive astrocytosis in time- and dose-dependent manners. The low-doses of PFOS increased the cell number and the expression of glial fibrillary acidic protein (GFAP), a well-known hallmark of reactive astrocytes, in C6 astrocyte cells. ELISA and RT-PCR analysis showed that PFOS promoted the expression and secretion of Interleukin-1 beta (IL-1β) in dose- and time-dependent manners. Furthermore, PFOS exposure could induce the phosphorylation and degradation of IκBα, and the translocation of NF-κB p65 from the cytoplasm to the nucleus in C6 glioma cell line. Thus, the NF-кB signaling pathway can be activated after PFOS exposure. In addition, pretreatment with AKT inhibitor LY294002 could obviously attenuate PFOS-induced NF-κB activation and IL-1β secretion. Taken together, these results indicated that PFOS could facilitate reactive astrocytosis and the secretion of pro-inflammatory cytokines through AKT-dependent NF-κB signaling pathway. |
| Databáze: | OpenAIRE |
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